Table 1:

Literature review of studies on the gut microbiome in immune-mediated dry eye, including Sjögren’s syndrome

Author, yr	Case group(s)	Control group	Sequencing method	Diversity	Increased relative abundance in cases	Decreased relative abundance in cases
de Paiva, 2016	pSS (n=10), all female	Healthy controls from Human Microbiome Project (n=45), majority male and significantly younger	16S rRNA, V4	NA	Genera: Pseudobutyrivibrio, Escherichia/Shigella, Blautia, Streptococcus	Genera: Bacteroides, Parabacteroides, Faecalibacterium, Prevotella
Mandl, 2017	pSS (n=42)	Age- and sex-matched controls (n=35)	16S rRNA; 54 bacterial probes	NA	None	Genera: Alistipes, Bifidobacterium
van der Meulen, 2019	pSS (n=39); SLE (n=30)	General population controls (n=965), significantly younger and significantly more males	16S rRNA, V4 and 806R	Decreased alpha diversity; No difference in beta diversity	Phyla: Bacteroidetes, Proteobacteria; Genera Bacteroides, Alistipes; Species: Bacteroides vulgatus, Bacteroides uniformis, Bacteroides ovatus	Species: Clostridium sensu stricto
Cano-Ortiz, 2020	pSS (n=19), all female	Age-, sex-, BMI-matched healthy controls (n=19)	16S rRNA, V2-V9	Decreased alpha diversity; Beta diversity showed tighter clustering of cases compared to controls	Phyla: Bacteroidetes, Proteobacteria; Families: Clostridiaceae, Veillonellaceae, Prevotellaceae, Rikenellaceae, Odoribacteraceae, Enterobacteriaceae; Genera: Prevotella, Escherichia, Clostridium, Enterobacter, Veillonella, Streptococcus; Species: Clostridium clostridioforme, E. coli, Prevotella copri	Phyla: Firmicutes, Actinobacteria; Families: Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, Porphyromonadaceae, Bifidobacteriaceae; Genera: Bacteroides, Alistipes, Dorea, Parabacteroides, Blautia, Lachnospira, Roseburia, Faecalibacterium, Ruminococcus, Bifidobacterium; Species: Bacteroides fragilis, Parabacteroides distasonis, Dorea longicatena, Ruminococcus lactaris, Faecalibacterium prausnitzii
Mendez, 2020	pSS (n=10), sSS (n=3); early markers (n=8)	Healthy controls from stool bank (n=21), all male and significantly younger	16S rDNA, V4-V5	No difference in Shannon’s alpha diversity; Increased alpha diversity using Faith’s phylogenetic diversity; Beta diversity showed distinct clustering of controls compared to cases	Phyla: Bacteroidetes, Actinobacteria, Proteobacteria; Families: Actinomycetaceae, Eggerthellaceae, Lactobacillaceae, Akkermansiaceae, Coriobacteriaceae, Eubacteriaceae; Genera: Prevotella, Megasphaera, Parabacteroides	Phyla: Firmicutes; Orders Clostridiales, Bacteroides; Families: Ruminococcaceae, Lachnospiraceae; Genera: Faecalibacterium, Veillonella
Moon, 2020	pSS (n=10); environmental DE (n=14)	Healthy controls (n=12), unmatched but no significant difference in sex or age	16S rRNA, V3-V4	No difference in alpha diversity; Beta diversity showed separate clustering between cases and controls	Phyla: Bacteroidetes, Actinobacteria; Genera: Veillonella, Prevotella, Odoribacter, Alistipes	Classes: Clostridia; Genera: Bifidobacterium, Blautia, Dorea, Agathobacter, Subdoligranulum
Watane, 2021	pSS or sSS (n=5); early markers (n=5)	Healthy, young stool donor for FMT (n=1)	16S rDNA, V4-V5	Increased alpha diversity; Beta diversity showed separate clustering between cases and the control	Phyla: Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, Proteobacteria, Verrucomicrobia; Genera: Alistipes, Streptococcus, Blautia	Phyla: Euryarchaeota, Fusobacteria; Genera: Faecalibacterium, Prevotella, Ruminococcus

Abbreviation: pSS, primary Sjogren’s syndrome; sSS, secondary Sjogren’s syndrome; SLE, systemic lupus erythematosus; FMT, fecal microbial transplant; yr, year; NA, not available